Background - This proposal examines the functional neuroanatomy of interpersonal distress. Based on the premise that humans have a fundamental need to belong, this research is concerned with understanding how people process information when they believe that their interpersonal relations are at risk. This topic is important because there is overwhelming evidence of physical and mental health problems resulting from and contributing to interpersonal distress (e.g., depression, social anxiety). Using multiple methodologies, and working across levels of analysis, the proposed research has the potential to provide new insights into how interpersonal distress changes how people process information in a way that affects their mental health. Although some research examining the neural correlates of rejection is beginning to emerge, there are ambiguities in the literature regarding the involvement of specific brain regions (i.e., anterior cingulate cortex) in feelings of rejection. Given the importance of interpersonal distress to mental health, research is needed to delineate the brain processes involved in feelings of rejection and how this impacts emotion, cognition, and behavior. Specific Aims - The overarching goal of this research is to understand the impact of interpersonal distress on the brain and behavior. Specific aims include (a) characterizing the neural mechanisms for detecting and responding to interpersonal distress, which includes examining a network of brain regions including ventral and dorsal anterior cingulate cortex, amygdala, and medial prefrontal cortex, (b) examining individual differences in responsiveness to interpersonal distress by testing the hypothesis that some indivduals are particularly sensitive to cues of social exclusion, and (c) identifying the effects of interpersonal distress on cognition, affect, and behavior, such as greater attention to rejection cues, increased social memory, and greater adherence to social norms. Significance - Because interpersonal distress has been implicated in many mental and physical health disorders, this research will contribute to a better understanding of its neural correlates, as well as how it impacts cognition, affect, and behavior. Ultimately, this may inform psychological treatments for many mental health disorders, including depression, post-traumatic stress disorder and social phobia.